Letter for the article Identification of a Novel Mitochondrial tRNA Mutation in Chinese Family with Type 2 Diabetes Mellitus
致信《2 型糖尿病中国家族线粒体 tRNA 基因突变的鉴定》一文
{"title":"Mitochondrial Diabetes May Not Be the Only Phenotypic Presentation of the m.5826A>G mtDNA Variant [Letter]","authors":"Josef Finsterer","doi":"10.2147/pgpm.s481009","DOIUrl":"https://doi.org/10.2147/pgpm.s481009","url":null,"abstract":"Letter for the article Identification of a Novel Mitochondrial tRNA Mutation in Chinese Family with Type 2 Diabetes Mellitus","PeriodicalId":501056,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":"41 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141780448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction: Immune cell interactions and metabolic changes are crucial in determining the tumor microenvironment and affecting various clinical outcomes. However, the clinical significance of metabolism evolution of immune cell evolution in colorectal cancer (CRC) remains unexplored. Methods: Single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing data were acquired from TCGA and GEO datasets. For the analysis of macrophage differentiation trajectories, we employed the R packages Seurat and Monocle. Consensus clustering was further applied to identify the molecular classification. Immunohistochemical results from AOM and AOM/DSS models were used to validate macrophage expression. Subsequently, GSEA, ESTIMATE scores, prognosis, clinical characteristics, mutational burden, immune cell infiltration, and the variance in gene expression among different clusters were compared. We constructed a prognostic model and nomograms based on metabolic gene signatures identified through the MEGENA framework. Results: We found two heterogeneous groups of M2 macrophages with various clinical outcomes through the evolutionary process. The prognosis of Cluster 2 was poorer. Further investigation showed that Cluster 2 constituted a metabolically active group while Cluster 1 was comparatively metabolically inert. Metabolic variations in M2 macrophages during tumor development are related to tumor prognosis. Additionally, Cluster 2 showed the most pronounced genomic instability and had highly elevated metabolic pathways, notably those associated with the ECM. We identified eight metabolic genes (PRELP, NOTCH3, CNOT6, ASRGL1, SRSF1, PSMD4, RPL31, and CNOT7) to build a predictive model validated in CRC datasets. Then, a nomogram based on the M2 risk score improved predictive performance. Furthermore, our study demonstrated that immune checkpoint inhibitor therapy may benefit patients with low-risk. Discussion: Our research reveals underlying relationships between metabolic phenotypes and immunological profiles and suggests a unique M2 classification technique for CRC. The identified gene signatures may be key factors linking immunity and tumor metabolism, warranting further investigations.
Keywords: CRC, macrophages, metabolic classification, tumor immunity, prognosis model
{"title":"M2 Macrophage Classification of Colorectal Cancer Reveals Intrinsic Connections with Metabolism Reprogramming and Clinical Characteristics","authors":"Fengxing Huang, Youwei Wang, Yu Shao, Runan Zhang, Mengting Li, Lan Liu, Qiu Zhao","doi":"10.2147/pgpm.s458798","DOIUrl":"https://doi.org/10.2147/pgpm.s458798","url":null,"abstract":"<strong>Introduction:</strong> Immune cell interactions and metabolic changes are crucial in determining the tumor microenvironment and affecting various clinical outcomes. However, the clinical significance of metabolism evolution of immune cell evolution in colorectal cancer (CRC) remains unexplored.<br/><strong>Methods:</strong> Single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing data were acquired from TCGA and GEO datasets. For the analysis of macrophage differentiation trajectories, we employed the R packages Seurat and Monocle. Consensus clustering was further applied to identify the molecular classification. Immunohistochemical results from AOM and AOM/DSS models were used to validate macrophage expression. Subsequently, GSEA, ESTIMATE scores, prognosis, clinical characteristics, mutational burden, immune cell infiltration, and the variance in gene expression among different clusters were compared. We constructed a prognostic model and nomograms based on metabolic gene signatures identified through the MEGENA framework.<br/><strong>Results:</strong> We found two heterogeneous groups of M2 macrophages with various clinical outcomes through the evolutionary process. The prognosis of Cluster 2 was poorer. Further investigation showed that Cluster 2 constituted a metabolically active group while Cluster 1 was comparatively metabolically inert. Metabolic variations in M2 macrophages during tumor development are related to tumor prognosis. Additionally, Cluster 2 showed the most pronounced genomic instability and had highly elevated metabolic pathways, notably those associated with the ECM. We identified eight metabolic genes (PRELP, NOTCH3, CNOT6, ASRGL1, SRSF1, PSMD4, RPL31, and CNOT7) to build a predictive model validated in CRC datasets. Then, a nomogram based on the M2 risk score improved predictive performance. Furthermore, our study demonstrated that immune checkpoint inhibitor therapy may benefit patients with low-risk.<br/><strong>Discussion:</strong> Our research reveals underlying relationships between metabolic phenotypes and immunological profiles and suggests a unique M2 classification technique for CRC. The identified gene signatures may be key factors linking immunity and tumor metabolism, warranting further investigations. <br/><br/><strong>Keywords:</strong> CRC, macrophages, metabolic classification, tumor immunity, prognosis model<br/>","PeriodicalId":501056,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":"76 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141586099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Weihua Yu, Jionghuang Chen, Shengxi Jin, Xiaoxiao Fan, Xiujun Cai
Background: Obesity is reaching epidemic proportions in the developed world. The biosynthesis and degradation of human glycoproteins take place at the highest level in the liver. However, the association between glycosylation and the factors affecting obesity and metabolism-associated steatohepatitis (MASH) is still unclear. Materials and Methods: Gene expression data of liver samples from obese patients were retrieved from GSE83452 and GSE89632 databases. Difference analysis and machine learning were used to identify hub genes involved in glycosylation and associated with the response of weight loss treatment. A total of 7 glycosylation-related hub genes were identified and then subjected to correlation analysis, immune cells infiltration analysis and ROC (Receiver Operating Characteristic) analysis. We also evaluated the potential function of 7 hub genes in obesity patients. MASH mice were used to validate the glycosylation-related hub genes. Results: A total of 25 overlapped glycosylation-related genes were identified by DEGs analysis. ACER2, STX17, ARF5, GPC4, ENTPD5, NANP, and DPY19L2 were identified as hub genes. Among these hub genes, ACER2, STX17, ARF5, and ENTPD5 were also differential expressed in MASH patients. ENTPD5 showed increased transcription in obese MASH mice. Conclusion: The current study identified seven glycosylation-related genes, ACER2, STX17, ARF5, GPC4, ENTPD5, NANP, and DPY19L2, that might play key roles in the development of obesity. ENTPD5 might play a key role in the development of MASH. These findings provide fresh perspectives for expanding the investigation of obesity and MASH.
{"title":"Identification and Validation of Glycosylation-Related Genes in Obesity and MASH: Insights from Human Liver Samples and a High-Fat Diet Mouse Model","authors":"Weihua Yu, Jionghuang Chen, Shengxi Jin, Xiaoxiao Fan, Xiujun Cai","doi":"10.2147/pgpm.s463608","DOIUrl":"https://doi.org/10.2147/pgpm.s463608","url":null,"abstract":"<strong>Background:</strong> Obesity is reaching epidemic proportions in the developed world. The biosynthesis and degradation of human glycoproteins take place at the highest level in the liver. However, the association between glycosylation and the factors affecting obesity and metabolism-associated steatohepatitis (MASH) is still unclear.<br/><strong>Materials and Methods:</strong> Gene expression data of liver samples from obese patients were retrieved from GSE83452 and GSE89632 databases. Difference analysis and machine learning were used to identify hub genes involved in glycosylation and associated with the response of weight loss treatment. A total of 7 glycosylation-related hub genes were identified and then subjected to correlation analysis, immune cells infiltration analysis and ROC (Receiver Operating Characteristic) analysis. We also evaluated the potential function of 7 hub genes in obesity patients. MASH mice were used to validate the glycosylation-related hub genes.<br/><strong>Results:</strong> A total of 25 overlapped glycosylation-related genes were identified by DEGs analysis. ACER2, STX17, ARF5, GPC4, ENTPD5, NANP, and DPY19L2 were identified as hub genes. Among these hub genes, ACER2, STX17, ARF5, and ENTPD5 were also differential expressed in MASH patients. ENTPD5 showed increased transcription in obese MASH mice.<br/><strong>Conclusion:</strong> The current study identified seven glycosylation-related genes, ACER2, STX17, ARF5, GPC4, ENTPD5, NANP, and DPY19L2, that might play key roles in the development of obesity. ENTPD5 might play a key role in the development of MASH. These findings provide fresh perspectives for expanding the investigation of obesity and MASH.<br/><br/>","PeriodicalId":501056,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":"43 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141550650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abstract: Recent research findings have highlighted the pivotal roles played by lncRNAs in both normal human development and disease pathogenesis. LncRNAs are expressed in oocytes and early embryos, and their expression levels change dynamically once the embryonic genome is activated during early human embryonic development. Abnormal expression of lncRNAs was found in follicular fluid, granulosa cells and oocytes of patients, and these lncRNAs were related to cell proliferation and apoptosis, nuclear maturation and follicle development. The expression levels of some lncRNAs in cumulus cells demonstrate correlations with the quality of oocytes and early embryos. This paper aims to present a comprehensive overview of the influence of LncRNAs on the developmental process of human oocytes as well as their involvement in certain infertility-related diseases.
{"title":"Influence of Long Non-Coding RNAs on Human Oocyte Development","authors":"Leitong Wang, Baoshan Li, Dongkai Cheng","doi":"10.2147/pgpm.s449101","DOIUrl":"https://doi.org/10.2147/pgpm.s449101","url":null,"abstract":"<strong>Abstract:</strong> Recent research findings have highlighted the pivotal roles played by lncRNAs in both normal human development and disease pathogenesis. LncRNAs are expressed in oocytes and early embryos, and their expression levels change dynamically once the embryonic genome is activated during early human embryonic development. Abnormal expression of lncRNAs was found in follicular fluid, granulosa cells and oocytes of patients, and these lncRNAs were related to cell proliferation and apoptosis, nuclear maturation and follicle development. The expression levels of some lncRNAs in cumulus cells demonstrate correlations with the quality of oocytes and early embryos. This paper aims to present a comprehensive overview of the influence of LncRNAs on the developmental process of human oocytes as well as their involvement in certain infertility-related diseases.<br/><br/><strong>Keywords:</strong> cumulus cells, female infertility, lncRNA, oocyte<br/>","PeriodicalId":501056,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":"28 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141522770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Pharmacogenomics research is currently revolutionizing treatment optimization by discovering molecular markers. Medicines are the cornerstone of treatment for both acute and chronic diseases. Pharmacogenomics associated treatment response varies from 20% to 95%, resulting in from lack of efficacy to serious toxicity. Pharmacogenomics has emerged as a useful tool for therapy optimization and plays a bigger role in clinical care going forward. However, in Africa, in particular in Ethiopia, such studies are scanty and not generalizing. Therefore, the objective of this review was to outline such studies, generating comprehensive evidence and identify studied variants’ association with treatment responses in Ethiopian patients. Methods: The Joanna Briggs Institute’s updated 2020 methodological guidelines for conducting and guidance for scoping reviews were used. We meticulously adhered to the systemic review reporting items checklist and scoping review meta-analyses extension. Results: Two hundred twenty-nine possibly relevant studies were searched. These include: 64, 54, 21, 48 and 42 from PubMed, Scopus, Google Scholar, EMBASE, and manual search, respectively. Seventy-seven duplicate studies were removed. Thirty-nine papers were rejected with justification, whereas 58 studies were qualified for full-text screening. Finally 19 studies were examined. The primary pharmacogene that was found to have a significant influence on the pharmacokinetics of efavirenz was CYP2B6. Drug-induced liver injury has frequently identified toxicity among studied medications. Conclusion and Future Perspectives: Pharmacogenomics studies in Ethiopian populations are less abundant. The studies conducted focused on infectious diseases, specifically on HAART commonly efavirenz and backbone first-line anti-tuberculosis drugs. There is a high need for further pharmacogenomics research to verify the discrepancies among the studies and for guiding precision medicine. Systematic review and meta-analysis are also recommended for pooled effects of different parameters in pharmacogenomics studies.
{"title":"The Role of Pharmacogenomics Studies for Precision Medicine Among Ethiopian Patients and Their Clinical Implications: A Scoping Review","authors":"Kefyalew Ayalew Getahun, Dessie Abebaw Angaw, Mezgebu Silamsaw Asres, Wubayehu Kahaliw, Zelalem Petros, Solomon Mequanente Abay, Getnet Yimer, Nega Berhane","doi":"10.2147/pgpm.s454328","DOIUrl":"https://doi.org/10.2147/pgpm.s454328","url":null,"abstract":"<strong>Background:</strong> Pharmacogenomics research is currently revolutionizing treatment optimization by discovering molecular markers. Medicines are the cornerstone of treatment for both acute and chronic diseases. Pharmacogenomics associated treatment response varies from 20% to 95%, resulting in from lack of efficacy to serious toxicity. Pharmacogenomics has emerged as a useful tool for therapy optimization and plays a bigger role in clinical care going forward. However, in Africa, in particular in Ethiopia, such studies are scanty and not generalizing. Therefore, the objective of this review was to outline such studies, generating comprehensive evidence and identify studied variants’ association with treatment responses in Ethiopian patients.<br/><strong>Methods:</strong> The Joanna Briggs Institute’s updated 2020 methodological guidelines for conducting and guidance for scoping reviews were used. We meticulously adhered to the systemic review reporting items checklist and scoping review meta-analyses extension.<br/><strong>Results:</strong> Two hundred twenty-nine possibly relevant studies were searched. These include: 64, 54, 21, 48 and 42 from PubMed, Scopus, Google Scholar, EMBASE, and manual search, respectively. Seventy-seven duplicate studies were removed. Thirty-nine papers were rejected with justification, whereas 58 studies were qualified for full-text screening. Finally 19 studies were examined. The primary pharmacogene that was found to have a significant influence on the pharmacokinetics of efavirenz was CYP2B6. Drug-induced liver injury has frequently identified toxicity among studied medications.<br/><strong>Conclusion and Future Perspectives:</strong> Pharmacogenomics studies in Ethiopian populations are less abundant. The studies conducted focused on infectious diseases, specifically on HAART commonly efavirenz and backbone first-line anti-tuberculosis drugs. There is a high need for further pharmacogenomics research to verify the discrepancies among the studies and for guiding precision medicine. Systematic review and meta-analysis are also recommended for pooled effects of different parameters in pharmacogenomics studies.<br/><br/>","PeriodicalId":501056,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":"23 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141506721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: The IQ motif and Sec7 domain ArfGEF 2 (IQSEC2), an X-linked gene that encodes the BRAG1 protein, is a guanine nucleotide exchange factor for the ADP ribosylation factor (ARF) protein family in the small guanosine triphosphate (GTP) binding protein. Mutations in this gene result in disorders such as intellectual disability (ID) and epilepsy. In this study, we analyze the clinical features of two patients with IQSEC2-mutation-related disease and discuss their possible pathogenesis. Methods: The two patients were diagnosed with ID and epilepsy. Genetic testing was performed using whole-exome sequencing, and the three-dimensional protein structure was analyzed. UCSC Genome Browser was used to analyze the conservation of IQSEC2 in different species. We compared IQSEC2 expression in the proband families with that in a control group, as well as the expression of the postsynaptic identity protein 95 (PSD-95), synapse-associated protein 97 (SAP97), ADP ribosylation factor 6 (ARF-6), and insulin receptor substrate 53kDa (IRSP53) genes interacting with IQSEC2. Results: We identified two semi-zygote mutations located in conserved positions in different species: an unreported de novo mutation, C.3576C>A (p. Tyr1192&ast), and a known mutation, c.2983C>T (p. Arg995Trp). IQSEC2 mutations resulted in significant changes in the predicted three-dimensional protein structure, while its expression in the two probands was significantly lower than that in the age-matched control group, and IQSEC2 expression in proband 1 was lower than that in his family members. The expression levels of PSD-95, ARF-6, and SAP97, IRSP 53, which interact with IQSEC2, were also significantly different from those in the family members and age-matched healthy children. Conclusion: The clinical phenotype resulting from IQSEC2 mutations can be explained by the significant decrease in its expression, loss of function of the mutant protein, and change in the expression of related genes. Our results provide novel insights into the molecular phenotype conferred by the IQSEC2 variants.
{"title":"Preliminary Study on Clinical Characteristics and Pathogenesis of IQSEC2 Mutations Patients","authors":"Yun Ren, Xiaona Luo, Haiyan Tong, Simei Wang, Jinbin Yan, Longlong Lin, Yucai Chen","doi":"10.2147/pgpm.s455840","DOIUrl":"https://doi.org/10.2147/pgpm.s455840","url":null,"abstract":"<strong>Background:</strong> The IQ motif and Sec7 domain ArfGEF 2 (<em>IQSEC2</em>), an X-linked gene that encodes the BRAG1 protein, is a guanine nucleotide exchange factor for the ADP ribosylation factor (ARF) protein family in the small guanosine triphosphate (GTP) binding protein. Mutations in this gene result in disorders such as intellectual disability (ID) and epilepsy. In this study, we analyze the clinical features of two patients with <em>IQSEC2</em>-mutation-related disease and discuss their possible pathogenesis.<br/><strong>Methods:</strong> The two patients were diagnosed with ID and epilepsy. Genetic testing was performed using whole-exome sequencing, and the three-dimensional protein structure was analyzed. UCSC Genome Browser was used to analyze the conservation of <em>IQSEC2</em> in different species. We compared <em>IQSEC2</em> expression in the proband families with that in a control group, as well as the expression of the postsynaptic identity protein 95 (PSD-95), synapse-associated protein 97 (SAP97), ADP ribosylation factor 6 (ARF-6), and insulin receptor substrate 53kDa (<em>IRSP53</em>) genes interacting with <em>IQSEC2</em>.<br/><strong>Results:</strong> We identified two semi-zygote mutations located in conserved positions in different species: an unreported <em>de novo</em> mutation, C.3576C>A (p. Tyr1192&ast), and a known mutation, c.2983C>T (p. Arg995Trp). <em>IQSEC2</em> mutations resulted in significant changes in the predicted three-dimensional protein structure, while its expression in the two probands was significantly lower than that in the age-matched control group, and <em>IQSEC2</em> expression in proband 1 was lower than that in his family members. The expression levels of <em>PSD-95, ARF-6</em>, and <em>SAP97, IRSP 53</em>, which interact with <em>IQSEC2</em>, were also significantly different from those in the family members and age-matched healthy children.<br/><strong>Conclusion:</strong> The clinical phenotype resulting from <em>IQSEC2</em> mutations can be explained by the significant decrease in its expression, loss of function of the mutant protein, and change in the expression of related genes. Our results provide novel insights into the molecular phenotype conferred by the <em>IQSEC2</em> variants.<br/><br/>","PeriodicalId":501056,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":"23 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141165968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kun He, Meng-yi Xie, Xiao-jin Gao, Hao Wang, Jing-dong Li
Introduction: Hepatocellular carcinoma (HCC) is one of the major types of liver cancer. Previous studies have shown that the centromere protein family is associated with malignant biological behaviors such as HCC proliferation. As a member of the centromere protein family, centromere protein Q (CENPQ) is closely associated with immunotherapy and immune cell infiltration in various tumors. However, the role and mechanism of CENPQ in HCC remain unclear. Methods: Multiple public databases and RT-qPCR were used to study the expression of CENPQ in HCC. Based on TCGA data, the correlation between CENPQ and clinicopathological characteristics and prognosis of HCC patients was analyzed, and its diagnostic value was evaluated. The potential biological functions of CENPQ in HCC were explored by functional enrichment analysis of differentially expressed genes. The distribution of tumor-infiltrating immune cell types was assessed using single-sample GSEA, and immune checkpoint gene expression was analyzed using Spearman correlation. Subsequently, loss-of-function experiments were performed to determine the function of CENPQ on the cell cycle and proliferation of HCC cells in vitro. Results: CENPQ was found highly expressed in HCC and correlated with weight, BMI, age, AFP, T stage, pathologic stage, histologic grade, and prothrombin time (all p < 0.05). ROC and Kaplan-Meier analyses indicated that CENPQ may be potentially used as a diagnostic marker for HCC (AUC = 0.881), and its upregulation is associated with decreased OS (p = 0.002), DSS (p < 0.001), and PFI (p = 0.002). Functional enrichment analysis revealed an association of CENPQ with biological processes such as immune cell infiltration, cell cycle, and hippo-merlin signaling deregulation in HCC. Furthermore, knockdown of CENPQ manifested in HCC cells with G0/1 phase cycle arrest and decreased proliferative capacity. Conclusion: CENPQ expression was higher in HCC tissues than in normal liver tissues. It was significantly associated with poor prognosis, immune cell infiltration, cell cycle, and proliferation. Therefore, CENPQ may become a promising prognostic biomarker for HCC patients.
Keywords: centromere protein Q, biomarker, immune infiltration, cell cycle, hepatocellular carcinoma
{"title":"The Correlation of Centromere Protein Q with Diagnosis and Prognosis in Hepatocellular Carcinoma","authors":"Kun He, Meng-yi Xie, Xiao-jin Gao, Hao Wang, Jing-dong Li","doi":"10.2147/pgpm.s456965","DOIUrl":"https://doi.org/10.2147/pgpm.s456965","url":null,"abstract":"<strong>Introduction:</strong> Hepatocellular carcinoma (HCC) is one of the major types of liver cancer. Previous studies have shown that the centromere protein family is associated with malignant biological behaviors such as HCC proliferation. As a member of the centromere protein family, centromere protein Q (CENPQ) is closely associated with immunotherapy and immune cell infiltration in various tumors. However, the role and mechanism of CENPQ in HCC remain unclear.<br/><strong>Methods:</strong> Multiple public databases and RT-qPCR were used to study the expression of CENPQ in HCC. Based on TCGA data, the correlation between CENPQ and clinicopathological characteristics and prognosis of HCC patients was analyzed, and its diagnostic value was evaluated. The potential biological functions of CENPQ in HCC were explored by functional enrichment analysis of differentially expressed genes. The distribution of tumor-infiltrating immune cell types was assessed using single-sample GSEA, and immune checkpoint gene expression was analyzed using Spearman correlation. Subsequently, loss-of-function experiments were performed to determine the function of CENPQ on the cell cycle and proliferation of HCC cells in vitro.<br/><strong>Results:</strong> CENPQ was found highly expressed in HCC and correlated with weight, BMI, age, AFP, T stage, pathologic stage, histologic grade, and prothrombin time (all p < 0.05). ROC and Kaplan-Meier analyses indicated that CENPQ may be potentially used as a diagnostic marker for HCC (AUC = 0.881), and its upregulation is associated with decreased OS (p = 0.002), DSS (p < 0.001), and PFI (p = 0.002). Functional enrichment analysis revealed an association of CENPQ with biological processes such as immune cell infiltration, cell cycle, and hippo-merlin signaling deregulation in HCC. Furthermore, knockdown of CENPQ manifested in HCC cells with G0/1 phase cycle arrest and decreased proliferative capacity.<br/><strong>Conclusion:</strong> CENPQ expression was higher in HCC tissues than in normal liver tissues. It was significantly associated with poor prognosis, immune cell infiltration, cell cycle, and proliferation. Therefore, CENPQ may become a promising prognostic biomarker for HCC patients.<br/><br/><strong>Keywords:</strong> centromere protein Q, biomarker, immune infiltration, cell cycle, hepatocellular carcinoma<br/>","PeriodicalId":501056,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":"223 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141165848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jun Mei Teng, Shuiqing Qin, Danyu Lu, Yefa Gu, Shi Jie Tang, Qiong Yan, Jiawei Yao, Chao Zhang
Purpose: To investigate the CYP2C19 genotype distribution and allelic frequency among the Zhuang and Han schizophrenic populations in Guangxi, examine the correlation between CYP2C19 genetic variants and standardized blood levels of Valproic Acid (VPA) in schizophrenic patients, and evaluate the effects of age, gender, and Body Mass Index (BMI) on standardized VPA blood concentrations. Patients and Methods: Between February and December 2022, 192 Zhuang and Han schizophrenia patients treated with VPA were studied. Steady-state VPA concentrations were determined using homogeneous enzyme immunoassays, and CYP2C19 &ast1, &ast2, and &ast3 loci via q-PCR. CYP2C19 genotype distributions between Zhuang and Han groups in Nanning were compared using chi-square tests and contrasted with other ethnicities. Non-parametric tests analyzed VPA variations, identifying critical factors through multivariate stepwise regression. Results: The study identified five CYP2C19 genotypes at the &ast2 and &ast3 loci, with the &ast3/&ast3 genotype absent in both cohorts. The CYP2C19 distribution in Guangxi Zhuang and Han mirrors, yet diverges significantly from Hui and Kazakh groups. Among 192 subjects, VPA blood levels remained consistent across metabolic types and ages 18– 60 but varied significantly by gender. Multivariate analysis revealed gender and BMI as significant factors, overshadowing CYP2C19 genotype and age. Conclusion: In Guangxi, CYP2C19 genetic variants in Zhuang and Han schizophrenia patients demonstrate statistically indistinguishable allelic and metabolic distributions. Gender and BMI can influence standardized VPA blood concentrations in schizophrenia patients. However, in our study cohort, the CYP2C19 genotype and age are not the primary determinants of standardized VPA blood levels.
Keywords:CYP2C19 gene, valproic acid, blood drug concentration, Zhuang Chinese, Han Chinese
{"title":"Evaluation of CYP2C19 Genetic Variant and Its Lack of Association with Valproic Acid Plasma Concentrations Among Zhuang and Han Schizophrenia Patients in Guangxi","authors":"Jun Mei Teng, Shuiqing Qin, Danyu Lu, Yefa Gu, Shi Jie Tang, Qiong Yan, Jiawei Yao, Chao Zhang","doi":"10.2147/pgpm.s457805","DOIUrl":"https://doi.org/10.2147/pgpm.s457805","url":null,"abstract":"<strong>Purpose:</strong> To investigate the <em>CYP2C19</em> genotype distribution and allelic frequency among the Zhuang and Han schizophrenic populations in Guangxi, examine the correlation between <em>CYP2C19</em> genetic variants and standardized blood levels of Valproic Acid (VPA) in schizophrenic patients, and evaluate the effects of age, gender, and Body Mass Index (BMI) on standardized VPA blood concentrations.<br/><strong>Patients and Methods:</strong> Between February and December 2022, 192 Zhuang and Han schizophrenia patients treated with VPA were studied. Steady-state VPA concentrations were determined using homogeneous enzyme immunoassays, and <em>CYP2C19</em> &ast1, &ast2, and &ast3 loci via q-PCR. <em>CYP2C19</em> genotype distributions between Zhuang and Han groups in Nanning were compared using chi-square tests and contrasted with other ethnicities. Non-parametric tests analyzed VPA variations, identifying critical factors through multivariate stepwise regression.<br/><strong>Results:</strong> The study identified five <em>CYP2C19</em> genotypes at the &ast2 and &ast3 loci, with the &ast3/&ast3 genotype absent in both cohorts. The <em>CYP2C19</em> distribution in Guangxi Zhuang and Han mirrors, yet diverges significantly from Hui and Kazakh groups. Among 192 subjects, VPA blood levels remained consistent across metabolic types and ages 18– 60 but varied significantly by gender. Multivariate analysis revealed gender and BMI as significant factors, overshadowing <em>CYP2C19</em> genotype and age.<br/><strong>Conclusion:</strong> In Guangxi, <em>CYP2C19</em> genetic variants in Zhuang and Han schizophrenia patients demonstrate statistically indistinguishable allelic and metabolic distributions. Gender and BMI can influence standardized VPA blood concentrations in schizophrenia patients. However, in our study cohort, the <em>CYP2C19</em> genotype and age are not the primary determinants of standardized VPA blood levels.<br/><br/><strong>Keywords:</strong> <em>CYP2C19</em> gene, valproic acid, blood drug concentration, Zhuang Chinese, Han Chinese<br/>","PeriodicalId":501056,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":"128 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140930166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objective: To investigate the association of smoking cessation intention and single nucleotide polymorphism of HDAC9 gene with LAA-S in Han people in Hainan province. Methods: A case-control study was conducted. Six single nucleotide polymorphisms (SNPS) of HDAC9 gene were genotyped by SNPscan genotyping technique in 248 patients with LAA-S and 237 controls in Hainan Han population. SNP loci (rs10227612, rs12669496, rs1548577, rs2074633, rs2526626, and rs2717344) were genotyped, and the genotype and allele frequencies were compared between the case and control group. At the same time, the distribution of smoking between the case and control group was compared, and the 3-year and 7-year follow-up smoking cessation between the case and control group was compared, so as to find out the effects of smoking cessation intention and HDAC9 SNP on LAA-S. Results: (1) The GT genotype at rs10227612, GG genotype at rs2717344, and GA genotype at rs1548577 in the case group were significantly higher than those in the control group, and the differences were statistically significant. (2) There were significant differences in the distribution of smoking between the case and control group (P < 0.05), and there were significant differences in the smoking cessation after 3 years and 7 years of follow-up between the case and control group (P < 0.05). The intention to quit smoking was positively correlated with the incidence of LAA-S. Conclusion: (1) The rs10227612, rs1548577, rs2074633, rs2717344 of HDAC9 gene may be significantly related to atherosclerotic cerebral infarction of great arteries in Hainan Han population, while rs12669496 and rs2526626 may not be related. (2) According to the statistics of smoking in the case and control group, smoking was related to large artery atherosclerotic cerebral infarction, and the intention to quit smoking was a very important factor affecting the success of smoking cessation.
Keywords:HDAC9, SNP, LAA-S, Hainan nationality, willingness to quit smoking
{"title":"To Investigate the Influence of Smoking Cessation Intention and Common Downstream Variants of HDAC9 Gene on Large Artery Atherosclerotic Cerebral Infarction","authors":"Lili Yu, Youwei Zhao","doi":"10.2147/pgpm.s453688","DOIUrl":"https://doi.org/10.2147/pgpm.s453688","url":null,"abstract":"<strong>Objective:</strong> To investigate the association of smoking cessation intention and single nucleotide polymorphism of <em>HDAC9</em> gene with LAA-S in Han people in Hainan province.<br/><strong>Methods:</strong> A case-control study was conducted. Six single nucleotide polymorphisms (SNPS) of HDAC9 gene were genotyped by SNPscan genotyping technique in 248 patients with LAA-S and 237 controls in Hainan Han population. SNP loci (rs10227612, rs12669496, rs1548577, rs2074633, rs2526626, and rs2717344) were genotyped, and the genotype and allele frequencies were compared between the case and control group. At the same time, the distribution of smoking between the case and control group was compared, and the 3-year and 7-year follow-up smoking cessation between the case and control group was compared, so as to find out the effects of smoking cessation intention and HDAC9 SNP on LAA-S.<br/><strong>Results:</strong> (1) The GT genotype at rs10227612, GG genotype at rs2717344, and GA genotype at rs1548577 in the case group were significantly higher than those in the control group, and the differences were statistically significant. (2) There were significant differences in the distribution of smoking between the case and control group (P < 0.05), and there were significant differences in the smoking cessation after 3 years and 7 years of follow-up between the case and control group (P < 0.05). The intention to quit smoking was positively correlated with the incidence of LAA-S.<br/><strong>Conclusion:</strong> (1) The rs10227612, rs1548577, rs2074633, rs2717344 of HDAC9 gene may be significantly related to atherosclerotic cerebral infarction of great arteries in Hainan Han population, while rs12669496 and rs2526626 may not be related. (2) According to the statistics of smoking in the case and control group, smoking was related to large artery atherosclerotic cerebral infarction, and the intention to quit smoking was a very important factor affecting the success of smoking cessation.<br/><br/><strong>Keywords:</strong> <em>HDAC9</em>, SNP, LAA-S, Hainan nationality, willingness to quit smoking<br/>","PeriodicalId":501056,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":"40 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140930214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abstract: Hepatocellular carcinoma (HCC) is the dominant type of liver cancers and is one of the deadliest health threats globally. The conventional therapeutic options for HCC are hampered by low efficiency and intolerable side effects. Gene therapy, however, now offers hope for the treatment of many disorders previously considered incurable, and gene therapy is beginning to address many of the shortcomings of conventional therapies. Herein, we summarize the involvement of genes in the pathogenesis and prognosis of HCC, with a special focus on dysregulated signaling pathways, genes involved in immune evasion, and non-coding RNAs as novel two-edged players, which collectively offer potential targets for the gene therapy of HCC. Herein, the opportunities and challenges of HCC gene therapy are discussed. These include innovative therapies such as genome editing and cell therapies. Moreover, advanced gene delivery technologies that recruit nanomedicines for use in gene therapy for HCC are highlighted. Finally, suggestions are offered for improved clinical translation and future directions in this area of endeavor.
{"title":"Understanding Gene Involvement in Hepatocellular Carcinoma: Implications for Gene Therapy and Personalized Medicine","authors":"Mahmoud A Younis, Hideyoshi Harashima","doi":"10.2147/pgpm.s431346","DOIUrl":"https://doi.org/10.2147/pgpm.s431346","url":null,"abstract":"<strong>Abstract:</strong> Hepatocellular carcinoma (HCC) is the dominant type of liver cancers and is one of the deadliest health threats globally. The conventional therapeutic options for HCC are hampered by low efficiency and intolerable side effects. Gene therapy, however, now offers hope for the treatment of many disorders previously considered incurable, and gene therapy is beginning to address many of the shortcomings of conventional therapies. Herein, we summarize the involvement of genes in the pathogenesis and prognosis of HCC, with a special focus on dysregulated signaling pathways, genes involved in immune evasion, and non-coding RNAs as novel two-edged players, which collectively offer potential targets for the gene therapy of HCC. Herein, the opportunities and challenges of HCC gene therapy are discussed. These include innovative therapies such as genome editing and cell therapies. Moreover, advanced gene delivery technologies that recruit nanomedicines for use in gene therapy for HCC are highlighted. Finally, suggestions are offered for improved clinical translation and future directions in this area of endeavor.<br/><br/><strong>Keywords:</strong> hepatocellular carcinoma, gene therapy, personalized medicine, nanomedicines, clinical translation<br/>","PeriodicalId":501056,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":"19 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140886758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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